Association between promoter polymorphisms of vascular endothelial growth factor gene and sporadic Alzheimer's disease among Northern Chinese Han.
ABSTRACT Increasing evidences suggest that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). In Northern Chinese Han, we found three polymorphisms in the VEGF promoter: -2578C/A (rs699947), -2549I/D (rs35569394) and -1154G/A (rs1570360). A strong linkage disequilibrium was detected between -2578C/A and -2549I/D. After adjusting the data by gender, age and the APOEepsilon4 status using logistic regression, the -1154G/G genotype was found to increase the risk for sporadic AD (SAD) by 1.4-folds. In the subgroup of APOEepsilon4 non-carriers, the -1154G allele and -2549D/-1154G haplotype were observed to be significantly higher in the 279 SAD patients than in the 317 healthy individuals. The present study provides the evidence that the -1154G allele and the -2549D/-1154G haplotype may be associated with the development of SAD in the individuals without APOEepsilon4 allele.
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ABSTRACT: Three regulatory SNPs (rSNPs) in the promoter region of the vascular endothelial growth factor-A (VEGFA) gene have been significantly associated with several human diseases or conditions. The rSNP alleles alter the DNA landscape for potential transcriptional factors to attach, resulting in changes in transcriptional factor binding sites (TFBS). These TFBS changes are examined with respect to the human diseases which have been found to be significantly associated with the rSNPs.The Journal of Physiological Sciences 10/2013; · 1.09 Impact Factor
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ABSTRACT: AIM: Conclusions on the association between polymorphisms in the vascular endothelial growth factor (VEGF) gene promoter and risk of Alzheimer's disease (AD) are ambiguous, and sufficient evaluation of the association is lacking. Therefore, we performed a meta-analysis of observational studies to explore the association between polymorphisms in the VEGF gene promoter and AD risk. METHODS: Bibliographical searches were performed in the MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases without any language limitations. Three investigators independently assessed abstracts for relevant studies and independently reviewed all eligible studies. A meta-analysis was conducted using a fixed- or random-effects model. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of association. All statistical analyses were performed using Stata 11.0 software. RESULTS: The meta-analysis of 2787 AD cases and 2841 controls from eight published case-control studies on the -2578C/A polymorphism and 1422 AD cases and 1063 controls from four studies on the -1154G/A polymorphism did not show any significant associations. However, in a subgroup analysis stratified by the presence of APOE є4, associations were observed with APOE ε4 (-) for -2578C/A (A vs. C: OR = 1.22, 95% CI = 1.04-1.43, P = 0.014; A/A vs. C/C: OR = 1.59, 95% CI = 1.11-2.27, P = 0.011 and A/A vs. A/C + C/C: OR = 1.46, 95% CI = 1.08-1.99, P = 0.015) and -1154G/A (A vs. G: OR = 0.74, 95% CI = 0.62-0.89, P = 0.001; A/A vs. G/G: OR = 0.57, 95% CI = 0.37-0.87, P = 0.009; A/G vs. G/G: OR = 0.69, 95% CI = 0.53-0.89, P = 0.004 and A/A + A/G vs. G/G: OR = 0.66, 95% CI = 0.52-0.85, P = 0.001). CONCLUSION: This meta-analysis showed the risk role of the -2578 polymorphism and the protective role of the -1154 polymorphism when the APOE є4 status was negative, suggesting that the two polymorphisms in the VEGF promoter may have opposing effects on AD risk in an APOE є4-independent manner.CNS Neuroscience & Therapeutics 04/2013; · 4.46 Impact Factor
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ABSTRACT: The purpose of this study was to evaluate the association of seven VEGF promoter polymorphisms with breast cancer risk in Punjabi population from North West India. We screened DNA samples of 102 sporadic breast cancer patients and 102 unrelated healthy, gender, and age-matched individuals for seven VEGF promoter polymorphisms [-417C/T (rs833062), -172C/A (rs59260042), -165C/T (rs79469752), -160C/T, -152G/A (rs13207351), -141A/C (rs28357093) and -116G/A (rs1570360)] by direct sequencing. The frequency of GG, GA, and AA genotype of -152G/A polymorphism was 26.47 vs 38.34 %, 46.08 vs 51.96 %, and 27.45 vs 9.80 %, in patients and controls, respectively. VEGF -152 AA genotype was significantly associated with increased risk for breast cancer (OR = 4.04, 95 %CI, 1.69-9.68, p = 0.001; recessive model OR = 3.48, 95 %CI, 1.59-7.63, p = 0.001). For VEGF -116G/A polymorphism, G and A allele frequencies were 65.2 vs 76.47 % and 34.8 vs 23.53 % in patients and controls, respectively. Individuals having -116AA genotype (OR = 3.40; 95 %CI, 1.24-9.37; p = 0.014) and A allele (OR = 1.73; 95 %CI, 1.12-2.67; p = 0.012) were associated with increased risk for breast cancer. VEGF -165C/T and -141A/C polymorphisms were associated with reduced risk for breast cancer. There was significantly decreased frequency of CT genotype (4.90 vs 18.63 %; p = 0.002) and T allele (2.45 vs 9.31 %; p = 0.003) of -165C/T polymorphism among breast cancer patients as compared to controls. VEGF -141A and C allele frequency were 96.57 vs 91.18 % and 3.43 vs 8.82 % in patients and controls, respectively. Significant reduced risk for breast cancer was observed with AC genotype (OR = 0.34, 95 %CI, 0.14-0.86; p = 0.019) and C allele (OR = 0.37; 95 %CI, 0.15-0.89; p = 0.023) of -141A/C polymorphism. We did not observe association of VEGF -417T/C, -172C/A, -160C/T polymorphisms with breast cancer risk in the studied subjects (p > 0.05). The VEGF -152G/A and -116G/A polymorphisms were found to be significantly associated with increased risk for breast cancer while -165C/T and -141A/C polymorphisms were found to be associated with decreased risk for breast cancer in Punjabi population from North West India.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 08/2014;